AncestryDNA COVID-19 Host Genetic Study Identifies Three Novel Loci

Abstract

Human infection with SARS-CoV-2, the causative agent of COVID-19, leads to a remarkably diverse spectrum of outcomes, ranging from asymptomatic to fatal. Recent reports suggest that both clinical and genetic risk factors may contribute to COVID-19 susceptibility and severity. To investigate genetic risk factors, we collected over 500,000 COVID-19 survey responses between April and May 2020 with accompanying genetic data from the AncestryDNA database. We conducted sex-stratified and meta-analyzed genome-wide association studies (GWAS) for COVID-19 susceptibility (positive nasopharyngeal swab test, ncases=2,407) and severity (hospitalization, ncases=250). The severity GWAS replicated associations with severe COVID-19 near ABO and SLC6A20 (P<0.05). Furthermore, we identified three novel loci with P<5x10-8. The strongest association was near IVNS1ABP, a gene involved in influenza virus replication, and was associated only in males. The other two novel loci harbor genes with established roles in viral replication or immunity: SRRM1 and the immunoglobulin lambda locus. We thus present new evidence that host genetic variation likely contributes to COVID-19 outcomes and demonstrate the value of large-scale, self-reported data as a mechanism to rapidly address a health crisis.

ABO Blood Types and COVID-19: Spurious, Anecdotal, or Truly Important Relationships? A Reasoned Review of Available Data

“…The majority of these studies were hypothesis-driven. Yet, six of them concerned genome-wide association studies (GWAS) that looked for genetic associations without a priori [ 5 , 20 , 23 , 26 , 27 , 37 ]. Of the latter, only one failed to observe a significant signal at the ABO locus on the long arm of chromosome 9 (9q34) [ 37 ].…”

“…The variations in ABO blood group frequencies between populations of different geographical origins and ancestries represent another important source of potential bias. In order to take this bias into account, in several studies, groups of patients and controls were stratified for ancestry [ 7 , 20 , 21 , 26 , 37 ]. Again, with the exception of one study discussed below [ 37 ], they consistently documented a lower risk of COVID-19 for blood group O, although not visible in all ethnic groups as illustrated by the study of Leaf et al who uncovered a significant ABO effect in the white American population, but not in minorities of African Americans or Latin Americans [ 7 ].…”

“…Thus, soon after the beginning of the pandemic a publication from Wuhan, China, reported a higher risk of infection for people of blood group A, and inversely a lower risk for people of blood group O [ 1 ]. Since then, associations with the ABO blood groups have been described in several additional publications from China as well as many other locations from Asia, the Middle East, Europe, and North America [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 ]. Associations between ABO phenotypes were described with either the risk of infection or disease severity, although most studies did not explicitly separate these two aspects.…”

An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia

“…population density and age structure), and personal health factors all play a major role in SARS-CoV-2 epidemiology (Balogun et al, 2020; Sattar Naveed et al, 2020; Scarpone et al, 2020). Additionally, several genetic loci that mediate SARS-CoV-2 susceptibility and severity have been found in contemporary European populations (Ellinghaus et al, 2020; Roberts et al, 2020), one of which contains a genetic variant that increases SARS-CoV-2 susceptibility that was likely introduced into the ancestors of modern Europeans after they interbred with Neanderthals ∼40,000 years ago (Zeberg and Pääbo, 2020). This historical admixture event has led to genetic differences within and between contemporary human populations that directly impact COVID-19 epidemiology – the Neanderthal-derived variant haplotype is now carried by 8% of modern Europeans, but at lower frequencies in African populations whose ancestors did not experience this admixture event – and suggests that evolutionary analyses of human populations may help reveal these genetic differences and ultimately assist in the development of novel drugs and therapies to combat the negative impacts of SARS-CoV-2.…”

Low Levels of Natural Anti-α-N-Acetylgalactosamine (Tn) Antibodies Are Associated With COVID-19

“…Indeed, group O individuals possess anti-A and anti-B antibodies that could have protected them from viral particles emitted by either blood group A or B patients. Interestingly, a large number of observations indicate that blood group O individuals have a lower risk of COVID-19, whereas blood group A individuals appear to be at a higher risk ( Cheng et al, 2005 ; Abdollahi et al, 2020 ; Ahmed et al, 2020 ; Aljanobi et al, 2020 ; Barnkob et al, 2020 ; Chegni et al, 2020 ; Delanghe et al, 2020 ; Dzik et al, 2020 ; Ellinghaus et al, 2020 ; Fan et al, 2020 ; Franchini et al, 2020 ; Gallian et al, 2020 ; Göker et al, 2020 ; Hoiland et al, 2020 ; Latz et al, 2020 ; Leaf et al, 2020 ; Li et al, 2020 ; Muniz-Diaz et al, 2020 ; Niles et al, 2020 ; Padhi et al, 2020 ; Ray et al, 2020 ; Roberts et al, 2020 ; Shelton et al, 2020 ; Sohlpour et al, 2020 ; Valenti et al, 2020 ; Wu et al, 2020 ; Zeng et al, 2020 ; Zhang et al, 2020 ; Zhao J. et al, 2020 ; Zietz et al, 2020 ). Only a few studies failed to find any association between ABO types and COVID-19, likely depending on study design ( Boudin et al, 2020 ; Focosi et al, 2020 ; Pairo-Castineira et al, 2020 ).…”